CT antigens are predominantly expressed in normal gametogenic tissues as well as in different histological types of tumors (Scanlan et al., 2002, Immunol Rev. 188:22-32. Review; Scanlan et al., 2004, Cancer Immun. 4:1. Review; Simpson et al., 2005, Nat Rev Cancer. 5(8):615-25. Review; Zendman et al., 2003, J Cell Physiol. 194(3):272-88. Review). In testis, CT antigens are expressed exclusively in cells of the germ cell lineage, although there is a marked variation in the protein expression pattern during different stages of sperm development. Likewise, a heterogeneous expression is also observed in tumors (Scanlan et al., 2002, Immunol Rev. 188:22-32. Review; Zendman et al., 2003, J Cell Physiol. 194(3):272-88. Review). Methylation status of the promoter region seems to be the main, but not the only regulator of their specific expression pattern (Scanlan et al., 2002, Immunol Rev. 188:22-32. Review; Simpson et al., 2005, Nat Rev Cancer. 5(8):615-25. Review; Zendman et al., 2003, J Cell Physiol. 194(3):272-88. Review). Most CT antigens have no defined biological function but their involvement in signaling, transcription, translation and chromosomal recombination has been proposed (Simpson et al., 2005, Nat Rev Cancer. 5(8):615-25. Review; Zendman et al., 2003, J Cell Physiol. 194(3):272-88. Review). It has also been proposed that the aberrant expression of CT antigens in tumors recapitulates portions of the germline gene expression programme and is related to some characteristics of the neoplastic phenotype such as immortality, invasiveness, immune evasion and metastatic capacity (Simpson et al., 2005, Nat Rev Cancer. 5(8):615-25. Review; Old, L J., 2001, Cancer Immun. 1:1).
Due to their restricted expression pattern, CT antigens are considered to be ideal targets for cancer immunotherapy (Scanlan et al., 2002, Immunol Rev. 188:22-32. Review; Bodey, 2002, Expert Opin Biol Ther. 2(6):577-84. Review). Indeed, a small subset of patients immunized with the known CT antigens MAGE-A and NY-ESO-1 have shown clinical benefits following immunization (Chen et al., 2004, Proc. Natl. Acad. Sci. U.S.A. 101: 9363-9368; Davis et al., 2004, Proc. Natl. Acad. Sci. U.S.A. 101:10697-10702; Jager et al., 2000, Proc. Natl. Acad. Sci. U.S.A. 97: 12198-12203; Marchand et al., 1999, Int. J. Cancer. 80: 219-230). However, because CT antigens are expressed in only a small subset of human tumors and in only a fraction of cases of a given tumor type, the identification of additional CT antigens is crucial for improving current immunotherapy protocols. Presently, 44 distinct CT-antigen families have been described, of which several have multiple members resulting in a total of 89 transcripts (Simpson et al., 2005, Nat Rev Cancer. 5(8):615-25. Review).
The identification of additional CT antigens and other genes having a tumor-associated expression profile is needed for the development of additional therapeutics and diagnostics to permit effective treatment and diagnosis of a broader group of cancer patients.